Altered AP-1 (activating protein-1) activity and c-jun activation in T cells exposed to the amide class herbicide 3,4-dichloropropionanilide (DCPA).

3,4-Dichloropropionanilide (DCPA), the active ingredient of some postemergence herbicides, has been demonstrated to inhibit several immune system functions including cytokine production by T cells. The central role of cytokines in regulating the immune response suggests a possible mechanism by which DCPA inhibits the immune system. Since interleukin (IL)-2 is critical in regulating many immune functions, we chose to investigate the effect of DCPA on this cytokine. Using the human T lymphoma line, Jurkat, stimulated with phorbol-12-myristate acetate (PMA) and the calcium ionophore A23187 (Io), we determined that DCPA exposure decreased IL-2 secretion and mRNA levels in a dose dependent manner. We hypothesized that DCPA affected one or more of the transcription factors that regulate IL-2 gene transcription. Activating protein 1(AP-1) is a transcription factor that has been demonstrated to be required for optimal IL-2 gene transcription. Electrophoretic mobility shift assays (EMSAs) demonstrated a decreased level of AP-1 DNA binding activity in DCPA-exposed Jurkat cells compared to control cells from 30 min to 2 h after stimulation. The altered AP-1 DNA binding kinetics was associated with a decrease in c-jun protein in these cells at 1 and 2 h after exposure and a decreased level of phosphorylated c-jun at 1-4 h after exposure. These results suggest a possible mechanism for DCPA-induced IL-2 inhibition; alteration in the activation of the c-jun component of AP-1.